Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and children and is also a predictable cause of respiratory illness in persons of all ages. Despite advances in our understanding of RSV pathogenesis and immune response, efforts to develop an RSV vaccine have been unsuccessful. Based on RSV infections in humans and rodent challenge models, it is reasonable to predict that a successful RSV vaccine candidate will induce neutralizing antibody responses against the RSV fusion (F) protein and also induce Th1-dominant cellular responses. As a novel approach towards an RSV vaccine, we plan to exploit the unique biophysical and immunological properties of the human papillomavirus (HPV) L1 and L2 capsid proteins. L1 by itself or in concert with L2 self-assemble into virus-like particles (VLPs) which elicit a broad array of immune responses. Based on the safety and efficacy data from large-scale clinical studies, HPV VLPs have recently been licensed as a subunit vaccine against cervical cancer. HPV VLPs may function as self-adjuvanting antigen delivery platforms that elicit humoral and Th1 cellular responses against heterologous antigens. Thus, we propose to generate HPV capsid proteins that bear portions of the RSV F protein and test the immunogenicity and protective efficacy of chimeric HPV/RSV VLPs in murine challenge models. This application utilizes the investigators'collective expertise in molecular biology, vaccine development, and virological and immunological aspects of HPV and RSV. PUBLIC HEALTH RELEVANCE: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and children and is also a predictable cause of respiratory illness in persons of all ages. The proposed project may provide substantial progress towards the development of an RSV vaccine, which remains an unmet medical need.